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Neutrophil extracellular traps mediate bone erosion in rheumatoid arthritis by enhancing RANKL-induced osteoclastogenesis.
Schneider, Ayda Henriques; Taira, Thaise Mayumi; Públio, Gabriel Azevedo; da Silva Prado, Douglas; Donate Yabuta, Paula Barbim; Dos Santos, Jéssica Cristina; Machado, Caio Cavalcante; de Souza, Flávio Falcão Lima; Rodrigues Venturini, Lucas Gabriel; de Oliveira, Renê Donizeti Ribeiro; Cunha, Thiago Mattar; Alves-Filho, José Carlos; Louzada-Júnior, Paulo; Aparecida da Silva, Tarcília; Fukada, Sandra Yasuyo; Cunha, Fernando Queiróz.
Afiliación
  • Schneider AH; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Taira TM; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Públio GA; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • da Silva Prado D; Department of Bio-Molecular Sciences, School of Pharmaceutical Science, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Donate Yabuta PB; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Dos Santos JC; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Machado CC; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • de Souza FFL; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Rodrigues Venturini LG; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • de Oliveira RDR; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Cunha TM; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Alves-Filho JC; Department of Neurosciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Louzada-Júnior P; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Aparecida da Silva T; Department of Medicine, Clinical Immunology Division, Medicine Faculty of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Fukada SY; Center of Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
  • Cunha FQ; Department of Medicine, Clinical Immunology Division, Medicine Faculty of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, Brazil.
Br J Pharmacol ; 181(3): 429-446, 2024 02.
Article en En | MEDLINE | ID: mdl-37625900
BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause bone erosion due to increased osteoclastogenesis. Neutrophils involvement in osteoclastogenesis remains uncertain. Given that neutrophil extracellular traps (NETs) can act as inflammatory mediators in rheumatoid arthritis, we investigated the role of NETs in stimulating bone loss by potentiating osteoclastogenesis during arthritis. EXPERIMENTAL APPROACH: The level of NETs in synovial fluid from arthritis patients was assessed. Bone loss was evaluated by histology and micro-CT in antigen-induced arthritis (AIA)-induced WT mice treated with DNase or in Padi4-deficient mice (Padi4flox/flox LysMCRE ). The size and function of osteoclasts and the levels of RANKL and osteoprotegerin (OPG) released by osteoblasts that were incubated with NETs were measured. The expression of osteoclastogenic marker genes and protein levels were evaluated by qPCR and western blotting. To assess the participation of TLR4 and TLR9 in osteoclastogenesis, cells from Tlr4-/- and Tlr9-/- mice were cultured with NETs. KEY RESULTS: Rheumatoid arthritis patients had higher levels of NETs in synovial fluid than osteoarthritis patients, which correlated with increased levels of RANKL/OPG. Moreover, patients with bone erosion had higher levels of NETs. Inhibiting NETs with DNase or Padi4 deletion alleviated bone loss in arthritic mice. Consistently, NETs enhanced RANKL-induced osteoclastogenesis that was dependent on TLR4 and TLR9 and increased osteoclast resorptive functions in vitro. In addition, NETs stimulated the release of RANKL and inhibited osteoprotegerin in osteoblasts, favouring osteoclastogenesis. CONCLUSIONS AND IMPLICATIONS: Inhibiting NETs could be an alternative strategy to reduce bone erosion in arthritis patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Trampas Extracelulares Límite: Animals / Humans Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Trampas Extracelulares Límite: Animals / Humans Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido